In order to dissect the molecular mechanisms whereby HIV-1 functionally alters or kills CD4+ T lymphocytes, transfected Jurkat cell lines expressing different HIV-1 proteins were established. Cells constitutively expressing functional qpl20 and qp4l showed no direct alterations in their cell growth and did not spontaneously fuse. In contrast, HIV-infected cells or HIV-envelope transfected cells could be induced to form syncytium and die upon co-culture with naive CD4+ cells. Such infected or transfected cells undergoing cell fusion and cell death displayed dramatic alterations in their intracellular signalling pathways as evidenced by changes in tyrosine phosphorylation of intracellular substrates. Blockade of these phosphorylations with an inhibitor of protein tyrosine phosphorylation, herbimycin A, dramatically reduced the cytopathicity associated with HIV-1. While proteins of about 95 and 30 kilodaltons were most dramatically tyrosine phosphorylated during HIV-1 cell fusion, the phosphorylation of the smaller substrate correlated most closely with syncytium formation and cell death. This protein was identified as the cyclin dependent kinase cdc2, a central regulator of cell cycle which is inhibited by tyrosine phosphorylation. The heavy and light chain antibody genes derived from two human anti-HIV envelope qp4l monoclonal cell lines were cloned, sequenced, and functionally expressed in recipient B cell lines. The genes from one of the two monoclonal lines conferred anti-gp4l specificity to transfected cell lines. The heavy and light chain variable region genes from this antibody (98-6) were genetically linked to the T cell receptor (TCR) constant alpha and beta regions, respectively to generate chimeric antibody/TCR genes. when these chimeric TCR genes were expressed in T lymphocytes, they conferred TCR-dependent activation function to the cells.